Nathaniel Kan

Perspectives on Science
12/04/01

1. What are meant by the primary, secondary, and tertiary structures of a protein?

Primary structure is the sequence of amino acids in a protein. Secondary structure is the
repeating patterns of those sequences, which often take the form of alpha helices, beta
sheets, and proline helices. Tertiary structure describes how those alpha helices, beta
sheets, and proline helices fit together in space.

2. New functional proteins can be derived by combining two processes: protein grafting
and molecular evolution. Describe each process and indicate what advantages each
process offers.

Protein grafting describes a process where the amino acids which form the bonding site
of one protein are taken and affixed to another protein which has a desirable structure.
This allows the creator much more control over synthesized proteins and the use of a
known bonding sequence.

Molecular evolution describes when proteins are used which are variants of a protein
with a desired structure. Millions of these mutant proteins are attached to a “phage” virus
encoded to produce more of the protein it is attached to. Then, these protein are placed on
a surface which contains the substance one desires the protein to interact with. Then, the
protein are washed away, except for the few which interact the best. This produces a new
generation of protein which interact better. The process is repeated until the evolution
produces a desirable protein. The advantage to this is that millions of different
possibilities will be tried every time the “phage” process is done, far more than ever
could be engineered and tried one-by-one. Unfortunately, this process is much more
expensive than protein grafting.

3. What is meant by "the protein folding problem"? Why has this problem been so
difficult to solve?

The sequence of amino acids in a protein determine the way a protein is folded.
Unfortunately, this is practically impossible to predict. The interactions which cause a
protein to fold a certain way are large in number but very small in individual effect. This
makes models almost impossible.
4. In regard to the specificity of protein-DNA interactions:
How many distinguishable hexanucleotide sequences are there in DNA?
How many distinguishable hexapeptide sequences are there in naturally
occurring proteins?
What structural feature of the DNA double helix is commonly
"recognized" by DNA-binding proteins?

There are 46 distinguishable hexanucleotide sequences in DNA.

There are 206 distinguishable hexapeptide sequences in naturally occurring proteins.

The structural feature of a DNA double helix which is commonly recognized by DNA-
binding proteins is he high electronegativity of the oxygens in the backbone. This means
that any protein with positive charge will bind DNA, but non-specifically.

Also, the outer edges of the double helix form a shape which is physically recognized by
some proteins. The way the proteins are shaped allows them to fit to the double helix
structure of the DNA.